Overview of Ertugliflozin Vivianne K

Total Page:16

File Type:pdf, Size:1020Kb

Overview of Ertugliflozin Vivianne K CLINICAL PHARMACOLOGY UPDATE Overview of Ertugliflozin Vivianne K. Nguyen and John R. White, Jr. Introduction combinations with the DPP-4 sita- espite the availability of 12 gliptin (brand name Stegujan) or with different classes of medica- metformin (brand name Segluromet). Dtions, many people with type Ertugliflozin is not approved for the 2 diabetes struggle to maintain gly- treatment of type 1 diabetes, renal im- cemic control (1). Among the many pairment, or ketoacidosis. new antidiabetic medications to have Mechanism of Action emerged in recent years, sodium– As other SGLT2 inhibitors, ertug- glucose cotransporter 2 (SGLT2) liflozin works by blocking glucose inhibitors have proved to be a par- transport from the glomerular filtrate ticularly effective oral treatment for across the apical membrane of the these patients (2). Since the approval proximal epithelial cells, resulting in of the first drug in this class, canagli- increased urinary glucose excretion flozin, by the U.S. Food and Drug and reduced filtered glucose renal re- Administration (FDA) in March absorption. Ertugliflozin is predom- 2013, a total of four SGLT2 agents inantly metabolized by the enzymes have become available (both as single UGT1A9 and UGT2B, with minor and fixed-dose combination formu- contributions by CYP3A4, and even las) (1). In 2017, an estimated 1.7 less by CYP3A5 and CYP2C8 (4). million patients received a dispensed Ertugliflozin does not inhibit CYP450 prescription for an SGLT2 inhibitor isoenzymes (CYPs) 1A2, 2C9, 2C19, from U.S. outpatient retail pharmacies 2C8, 2B6, 2D6, or 3A4 and does not (2). Ertugliflozin is the newest agent induce CYPs 1A2, 2B6, or 3A4 (4). among these, having received FDA This might be beneficial in patients approval in December 2017 (3). with type 2 diabetes who have com- Indications plications and are on multiple med- Ertugliflozin is indicated as an adjunct ications because taking ertugliflozin to diet and exercise for control of hy- would reduce the chance of having perglycemia in adults (≥18 years of major interactions with drugs that age) with type 2 diabetes (4). It can are metabolized by these common College of Pharmacy and Pharmaceutical enzymes (2). Sciences, Washington State University, be used as monotherapy in patients Spokane, WA for whom metformin is contraindi- Potential Advantages Corresponding author: John R. White, Jr., cated or not well tolerated. It can also Ertugliflozin has been shown to lower [email protected] be used in combination with other A1C in adults with type 2 diabetes. It https://doi.org/10.2337/cd18-0097 antidiabetic agents (most commonly has been studied extensively in multi- metformin or a dipeptidyl peptidase ple clinical trial settings and has been ©2018 by the American Diabetes Association. Readers may use this article as long as the work 4 [DPP-4] inhibitor) to help reduce found to be effective in all of them is properly cited, the use is educational and not A1C. Currently, ertugliflozin is avail- (5). Three multicenter, randomized, for profit, and the work is not altered. See http:// creativecommons.org/licenses/by-nc-nd/3.0 able as an oral tablet sold under the double-blind, placebo- and active for details. brand name Steglatro or in oral tablet comparator–controlled clinical studies 176 CLINICAL.DIABETESJOURNALS.ORG NGUYEN AND WHITE evaluating ertugliflozin have demon- in patients taking an SGLT2 inhibi- not achieved their glycemic goals. strated its efficacy in further lower- tor. Twelve cases have been identified Patients’ medical history, costs, and ing A1C when used in combination since 2013 in both male and female risk/benefit factors are key issues that with sitagliptin in 1,985 people with patients who were being treated with should be thoroughly considered be- type 2 diabetes from different ethnic an SGLT2 inhibitor (1). Ertugliflozin fore starting patients on ertugliflozin groups (6). Another phase 3 trial in has included this information in its therapy. 4,800 people with type 2 diabetes and package insert, and patients being moderate renal failure compared the treated with this medication will be Duality of Interest use of ertugliflozin as monotherapy monitored closely in its post-market- J.R.W. serves on an advisory board for and in combination with metformin ing surveillance. Sanofi. No other potential conflicts of inter- est relevant to this article were reported. or sitagliptin, as well as insulin and Cost a sulfonylurea. Results confirmed sig- The out-of-pocket price of ertuglifloz- nificantly lower A1C in those who Author Contributions in monotherapy tablets is $321.99 per took ertugliflozin alone or in combi- Both authors contributed to and were 30-tablet bottle for 1 month of use involved in the research, writing, and editing nation with sitagliptin (6). based on recommended dosing (6). of this article. J.R.W. is the guarantor of this Ertugliflozin therapy may also be work and, as such, had full access to all of Currently, Merck has a copayment beneficial for patients who are over- the references cited and takes responsibility assistance program that will help cover for the accuracy of the content. weight or hypertensive. Due to its some of patients’ out-of-pocket cost if mechanism of action, ertugliflozin private insurance is used to fill a pre- References induces more excretion of sodium scription for ertugliflozin or its com- 1. U.S. Food and Drug Administration. through osmotic diuresis, which then Drug safety and availability: FDA warns bination formulations with sitagliptin leads to a mild reduction in blood about rare occurrences of a serious infection or metformin. of the genital area with SGLT2 inhibitors pressure. Excretion of glucose in the for diabetes. Available from www.fda. urine also helps with weight loss due Commentary gov/Drugs/DrugSafety/ucm617360.htm. to loss of calories (7). Another study Given its risk/benefit profile, ertugli- Accessed 5 October 2018 of ertugliflozin has shown it to be flozin is considered a favorable drug 2. U.S. Food and Drug Administration. Steglatro (ertugliflozin), Steglujan associated with a mean reduction in of choice within the SGLT2 inhibi- (ertugliflozin and sitagliptin), Segluromet body weight of 6.6 lb with the 5-mg tor class of medications. It does not (ertugliflozin and metformin hydro- dose compared to 2.2 lb with placebo contain a black box warning, as does chloride) tablets. Available from www. accessdata.fda.gov/drugsatfda_docs/ (7). More data are being collected to canagliflozin for its risk of lower-limb nda/2017/209803,209805,209806 compare these benefits to those of amputation in people with type 2 di- Orig1s000TOC.cfm. Accessed 5 other SGLT2 inhibitors. abetes and established cardiovascular October 2018 Potential Disadvantages disease (CVD) (8). However, pre- 3. Pfizer. FDA approves SGLT2 inhibi- scribers must still consider carefully tor STEGLATRO™ (ertugliflozin) and Clinical trials have demonstrated that fixed-dose combination STEGLUJAN™ before starting this therapy in elderly the safety profile of ertugliflozin is (ertugliflozin and sitagliptin) for adults with patients with renal impairment and type 2 diabetes. Available from www.pfizer. similar to other compounds in its class CVD, those with recurrent infections com/news/press-release/press-release-detail/ (i.e., association with genital mycot- fda_approves_sglt2_inhibitor_steglatro_ and high risk of limb amputation, and ic infection, lower-limb amputation, ertugliflozin_and_fixed_dose_combination_ female patients with recurrent urinary steglujan_ertugliflozin_and_sitagliptin_for_ urinary tract infection, acute kidney tract infections. adults_with_type_2_diabetes. Accessed 5 injury hypotension, and ketoacidosis) October 2018 Patient education is key before (5). Because this drug has been ap- starting this therapy. The FDA 4. U.S. Food and Drug Administration. proved recently, data used to evaluate Medication guide: Steglujan (STEG-loo-jan) released a safety announcement in its associated risks with regard to these (ertugliflozin and sitagliptin) tablets, for oral August 2018 to advise patients treated use. Available from www.accessdata.fda.gov/ adverse effects are still being collected with SGLT2 inhibitors to seek med- drugsatfda_docs/label/2018/209805s001lbl. and will be updated in the near future pdf#page=32. Accessed 5 April 2018 ical attention immediately if they (5). However, one could expect to see 5. Merck, Sharp & Dohme. Steglatro experience symptoms of redness, a range of adverse effects with ertugli- (ertugliflozin) official website. Available swelling, or tenderness of the genital from www.steglatro.com. Accessed 5 flozin similar to those of other SGLT2 areas accompanied by a fever (8). October 2018 inhibitors. 6. U.S. Food and Drug Administration. A recent safety announcement Bottom Line Englund E. Center for Drug Evaluation from the FDA (1) has raised con- Ertugliflozin seems to be a reasonable and Research application number 209803. Available from www.accessdata.fda.gov/ cern regarding the risk of Fournier’s second- or third-line therapeutic op- drugsatfda_docs/nda/2017/209803,209805, gangrene, a rare but life-threatening tion adjuvant to diet and exercise for 209806Orig1s000SumR.pdf. Accessed 25 bacterial infection of the genial areas, people with type 2 diabetes who have April 2018 VOLUME 37, NUMBER 2, SPRING 2019 177 CLINICAL PHARMACOLOGY UPDATE 7. Clements JM. New SGLT-2 inhibitor: 8. Micromedex Canagliflozin (Invokana). evidencexpert/ND_T/evidencexpert/ ertugliflozin (Steglatro) [blog post]. Available from www.micromedexsolutions. PFActionId/evidencexpert.GoToDashboard? Available from www.diabeteseducator.org/ com/micromedex2/librarian/CS/0ECE1D/ docId=930464&contentSetId=100&title= news/aade-blog/aade-blog-details/jennifer- ND_PR/evidencexpert/ND_P/evidence Canagliflozin&servicesTitle=Canagliflozin n.-clements-pharmd-bcps-cde-bcacp/2018/ xpert/DUPLICATIONSHIELDSYNC/ &brandName=Invokana#. Accessed 5 05/01/new-sglt-2-inhibitor-ertugliflozin. F4ADC7/ND_PG/evidencexpert/ October 2018 Accessed 5 October 2018 ND_B/evidencexpert/ND_AppProduct/ 178 CLINICAL.DIABETESJOURNALS.ORG.
Recommended publications
  • Steglujan, INN-Ertugliflozin-Sitagliptin
    25 January 2018 EMA/86941/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report Steglujan International non-proprietary name: ertugliflozin / sitagliptin Procedure No. EMEA/H/C/004313/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion ................................................................................ 9 2.1. Problem statement ............................................................................................... 9 2.1.1. Disease or condition ........................................................................................... 9 2.1.2. Epidemiology .................................................................................................... 9 2.1.3. Clinical presentation ..........................................................................................
    [Show full text]
  • Steglujan (Ertugliflozin/Sitagliptin), Segluromet
    Steglatro™ (ertugliflozin), Steglujan™ (ertugliflozin/sitagliptin), Segluromet™ (ertugliflozin/metformin) – New drug approval • On December 19, 2017, the FDA approved Merck’s Steglatro (ertugliflozin), Steglujan (ertugliflozin/sitagliptin), and Segluromet (ertugliflozin/metformin) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). — Steglujan is indicated when treatment with both ertugliflozin and sitagliptin is appropriate. — Segluromet is indicated when patients are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin. — These drugs are not recommended in patients with type 1 diabetes mellitus (T1DM) or for the treatment of diabetic ketoacidosis. — Steglujan has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Steglujan. • Ertugliflozin is the fourth sodium-glucose co-transoporter-2 (SGLT2) inhibitor approved by the FDA. Other marketed SGLT2 inhibitors include Jardiance® (empagliflozin), Farxiga® (dapagliflozin), and Invokana® (canagliflozin). • The efficacy and safety of ertugliflozin were evaluated in multiple clinical studies involving patients with T2DM. Ertugliflozin was studied as monotherapy and in combination with metformin and/or a dipeptidyl peptidase 4 (DPP-4) inhibitor. Ertugliflozin was also studied in combination with other antidiabetic medications, including insulin and a sulfonylurea, and in T2DM patients with moderate renal impairment. — In patients with T2DM, treatment with ertugliflozin, ertugliflozin + sitagliptin, and ertugliflozin + metformin reduced hemoglobin A1c (HbA1c) vs. placebo or the active comparator. — In patients with T2DM and moderate renal impairment, treatment with ertugliflozin did not result in a reduction in HbA1c vs.
    [Show full text]
  • SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease
    Journal of Clinical Medicine Editorial SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease Swetha R. Kanduri 1 , Karthik Kovvuru 1, Panupong Hansrivijit 2 , Charat Thongprayoon 3, Saraschandra Vallabhajosyula 4, Aleksandra I. Pivovarova 5 , Api Chewcharat 3, Vishnu Garla 6, Juan Medaura 5 and Wisit Cheungpasitporn 3,5,* 1 Department of Nephrology, Ochsner Medical Center, New Orleans, LA 70121, USA; [email protected] (S.R.K.); [email protected] (K.K.) 2 Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA 17105, USA; [email protected] 3 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA; [email protected] (C.T.); [email protected] (A.C.) 4 Section of Interventional Cardiology, Division of Cardiovascular Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; [email protected] 5 Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39156, USA; [email protected] (A.I.P.); [email protected] (J.M.) 6 Department of Internal Medicine and Mississippi Center for Clinical and Translational Research, University of Mississippi Medical Center, Jackson, MS 39156, USA; [email protected] * Correspondence: [email protected] Received: 20 August 2020; Accepted: 20 August 2020; Published: 24 August 2020 Abstract: Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism.
    [Show full text]
  • Newer Diabetes Treatments Drug Class Update with New Drug Evaluation: Semaglutide and Ertugliflozin
    © Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 | Fax 503-947-1119 Newer Diabetes Treatments Drug Class Update with New Drug Evaluation: Semaglutide and Ertugliflozin Date of Review: July 2018 Date of Last Review: September 2017 End Date of Literature Search: 05/23/2018 Generic Name: semaglutide Brand Name (Manufacturer): Ozempic® (Novo Nordisk) Generic Name: ertugliflozin, ertugliflozin/sitagliptin, ertugliflozin/metformin Brand Name (Manufacturer): Steglatro™, Steglujan™, Segluromet™ (Merck & Co., Inc.) Dossier Received: ertugliflozin (yes), semaglutide (no) Current Status of PDL Class: See Appendix 1. Purpose for Class Update: To evaluate the safety and efficacy of semaglutide and ertugliflozin (and combinations) which were recently approved for blood glucose lowering in patients with type 2 diabetes mellitus (T2DM). High quality new evidence published since the last review will also be presented. Research Questions: 1. In patients with T2DM, is there any new comparative evidence for non-insulin antidiabetic therapies based on surrogate efficacy outcomes (e.g., hemoglobin A1c [HbA1c]) and long-term clinically meaningful effectiveness outcomes (e.g., microvascular outcomes, macrovascular outcomes and mortality)? 2. In patients with T2DM, is there any new comparative evidence for non-insulin diabetes treatments based on harms outcomes (e.g., severe hypoglycemia, heart failure, diabetic ketoacidosis, pancreatitis, etc.)? 3. Are there subpopulations of patients with T2DM for which specific therapies may be more effective or associated with less harm? 4. What are the efficacy and harms evidence for the two new non-insulin diabetes treatments, ertugliflozin and semaglutide? Conclusions: A Drug Effectiveness Review Project (DERP) update on newer diabetes therapies, three new guidelines/standards, one new randomized controlled trial and two new drug reviews were reviewed for this class update.
    [Show full text]
  • PRODUCT INFORMATION Ipragliflozin Item No
    PRODUCT INFORMATION Ipragliflozin Item No. 22287 CAS Registry No.: 761423-87-4 OH Formal Name: (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien- 2-ylmethyl)-4-fluorophenyl]-D-glucitol OH Synonym: ASP1941 O MF: C21H21FO5S FW: 404.5 S OH Purity: ≥98% OH UV/Vis.: λmax: 231, 267 nm Supplied as: A crystalline solid F Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Ipragliflozin is supplied as a crystalline solid. A stock solution may be made by dissolving the ipragliflozin in the solvent of choice. Ipragliflozin is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide, which should be purged with an inert gas. The solubility of ipragliflozin in these solvents is approximately 30 mg/ml. Ipragliflozin is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, ipragliflozin should first be dissolved in ethanol and then diluted with the aqueous buffer of choice. Ipragliflozin has a solubility of approximately 0.13 mg/ml in a 1:7 solution of ethanol:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Ipragliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 7.4 nM in CHO cells expressing the human cotransporter).1 It is selective for SGLT2 over SGLT1, SGLT3, SGLT4, SGLT5, and SGLT6 (IC50s = 1.9, 30.4, 15.9, 0.46, and 10.4 µM, respectively). Ipragliflozin (0.1-3 mg/kg) decreases plasma levels of insulin and glucose in an oral glucose tolerance test in a mouse model of diabetes induced by high-fat diet, streptozotocin (STZ; Item No.
    [Show full text]
  • SEGLUROMET, INN-Ertugliflozin-Metformin
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Segluromet 2.5 mg/850 mg film-coated tablets Segluromet 2.5 mg/1,000 mg film-coated tablets Segluromet 7.5 mg/850 mg film-coated tablets Segluromet 7.5 mg/1,000 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Segluromet 2.5 mg/850 mg film-coated tablets Each tablet contains 2.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of metformin hydrochloride. Segluromet 2.5 mg/1,000 mg film-coated tablets Each tablet contains 2.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1,000 mg of metformin hydrochloride. Segluromet 7.5 mg/850 mg film-coated tablets Each tablet contains 7.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg metformin hydrochloride. Segluromet 7.5 mg/1,000 mg film-coated tablets Each tablet contains 7.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1,000 mg metformin hydrochloride. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet). Segluromet 2.5 mg/850 mg film-coated tablets Beige, 18 x 10 mm oval, film-coated tablet debossed with “2.5/850” on one side and plain on the other side. Segluromet 2.5 mg/1,000 mg film-coated tablets Pink, 19.1 x 10.6 mm oval, film-coated tablet debossed with “2.5/1000” on one side and plain on the other side.
    [Show full text]
  • SGLT2) Inhibitors (Gliflozins) in Adults with Type 2 Diabetes (T2DM
    Sodium-glucose cotransporter-2 (SGLT2) inhibitors (Gliflozins) in Adults with Type 2 Diabetes (T2DM) There are currently four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ertugliflozin) licensed in the UK for the management of adults with T2DM. No head to head trials between the SGLT2 inhibitors have been conducted. As at December 2019, clinical outcome data is available for three of the four SGLT2 inhibitors around their cardiovascular effects in people with T2DM. Ertugliflozin is still to report on this data. This document summarises the key prescribing considerations. NICE Technology Appraisal Recommendation NICE makes recommendations for when SGLT2 inhibitors can be considered in adults with T2DM; Hertfordshire Medicines Management Committee Recommendations are in line with NICE guidance: Monotherapy NICE TA 390: Canagliflozin, Dapagliflozin and Empagliflozin and NICE TA 572: Ertugliflozin as monotherapies for treating T2DM Monotherapy recommended as option in adults for whom metformin is contraindicated or not tolerated and when diet & exercise alone do not provide adequate glycaemic control, only if: •a DPP‑4 inhibitor would otherwise be prescribed and •a sulfonylurea or pioglitazone is not appropriate. Dual therapy NICE TA 315: Canagliflozin, NICE TA288: Dapagliflozin, TA 336: Empagliflozin, TA 572: Ertugliflozin as combination therapies for treating T2DM In a dual therapy regimen in combination with metformin is recommended as an option, only if: •a sulfonylurea is contraindicated or not tolerated or •the person is at significant risk of hypoglycaemia or its consequences. In combination with insulin NICE TA 315: Canagliflozin, NICE TA288: Dapagliflozin, TA 336: Empagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option.
    [Show full text]
  • SGLT2 Inhibitors in Combination Therapy: from Mechanisms To
    Diabetes Care Volume 41, August 2018 1543 Michael¨ J.B. van Baar, SGLT2 Inhibitors in Combination Charlotte C. van Ruiten, Marcel H.A. Muskiet, Therapy: From Mechanisms to Liselotte van Bloemendaal, Richard G. IJzerman, and PERSPECTIVES IN CARE Clinical Considerations in Type 2 Daniel¨ H. van Raalte Diabetes Management Diabetes Care 2018;41:1543–1556 | https://doi.org/10.2337/dc18-0588 The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained. With guidelines moving away from a one-size-fits-all approach toward setting patient-centered goals and allowing flexibility in choosing a second-/ third-line drug from the growing number of U.S. Food and Drug Administration– approved glucose-lowering agents, keen personalized management in T2D has become a challenge for health care providers in daily practice. Among the newer generation of glucose-lowering drug classes, sodium–glucose cotransporter 2 inhibitors (SGLT2is), which enhance urinary glucose excretion to lower hyper- glycemia, have made an imposing entrance to the T2D treatment armamentarium. Given their unique insulin-independent mode of action and their favorable efficacy– to–adverse event profile and given their marked benefits on cardiovascular-renal outcome in moderate-to-high risk T2D patients, which led to updates of guidelines and product monographs, the role of this drug class in multidrug regimes is promising. However, despite many speculations based on pharmacokinetic and pharmacodynamic properties, physiological reasoning, and potential synergism, the effects of these agents in terms of glycemic and pleiotropic efficacy when combined with other glucose-lowering drug classes are largely understudied.
    [Show full text]
  • ANTI-HYPERGLYCEMIC DIABETES AGENTS in T2DM: Color Outcomes Comparison Summary Table
    ANTI-HYPERGLYCEMIC DIABETES AGENTS in T2DM: Outcomes Comparison Summary Table L Regier BSP BA, M LeBras PharmD, T Trischuk PharmD, J Bareham BSP, L Lu BSP © www.RxFiles.ca Aug 2021 Drug Class Sulfonylureas TZDs Meglitinides DPP4 Inhibitors GLP1 Agonists *** SGLT2 Inhibitors *** Insulin in T2DM Generic Metformin Gliclazide Glyburide Pioglitazone Rosiglitazone Acarbose Repaglinide Saxagliptin ONGLYZA Liraglutide VICTOZA Empagliflozin JARDIANCE Intensity: Intensity: BRAND (MF) DIAMICRON DIABETA ACTOS, g AVANDIA GLUCOBAY GLUCONORM Sitagliptin JANUVIA Exenatide BYETTA, BYDUREON Canagliflozin INVOKANA Less More GLUCOPHAGE Dulaglutide TRULICITY Dapagliflozin FORXIGA, FARXIGA Alogliptin NESINA (e.g. NPH (Multiple daily GLUCOTROL D/C STEGLATRO Glipizide Nateglinide Semaglutide OZEMPIC, RYBELSUS (PO) Ertugliflozin Linagliptin TRAJENTA HS + MF) doses) STARLIX D/C SPREAD-DIMCAD] Lixisenatide ADLYXINE; ALBIGLUTIDE D/C SAVOR-TIMI 53, EMPA-REG, CANVAS, CREDENCE, T2DM: UKPDS-33,80; ADVANCE, Major trials to UKPDS- ProACTIVE ACE 33,34,80 UKPDS- Meta-analysis. TECOS, EXAMINE LEADER, EXSCEL, FREEDOM CVO, DECLARE, VERTIS-CV (2020), ACCORD, VADT, ORIGIN, DEVOTE support ADVANCE (Prevention (ADOPT; 33,80 Ferwana M. Meta- RECORD interim, PROLOGUE, REWIND, SUSTAIN-6, PIONEER-6, DAPA-HF, DAPA-CKD (2020), T1DM: DCCT/EDIC findings/ analysis 2013. trial: Stop- - some use in (ADOPT) ADOPT, DREAM CARMELINA, EMPEROR-Reduced & -Preserved (Also Boussageon et al. Meta- Outcomes* ADVANCE) SR-Liao 2017; IRIS NIDDM) ELIXA, HARMONY CAROLINA (2020), EMPA-Kidney (2022) analysis.
    [Show full text]
  • STEGLUJAN Safely and Effectively
    therapy in clinical situations known to predispose to ketoacidosis. HIGHLIGHTS OF PRESCRIBING INFORMATION (5.3) These highlights do not include all the information needed to use • Acute Kidney Injury and Impairment in Renal Function: Consider STEGLUJAN safely and effectively. See full prescribing temporarily discontinuing in settings of reduced oral intake or fluid information for STEGLUJAN. losses. If acute kidney injury occurs, discontinue and promptly treat. There have been postmarketing reports of acute renal failure in STEGLUJAN™ (ertugliflozin and sitagliptin) tablets, for oral use patients taking sitagliptin, sometimes requiring dialysis. Monitor Initial U.S. Approval: 2017 renal function. (5.4) • Urosepsis and Pyelonephritis: Evaluate patients for signs and ----------------------------INDICATIONS AND USAGE ---------------------------­ symptoms of urinary tract infections and treat promptly, if indicated. STEGLUJAN is a combination of ertugliflozin, a sodium glucose co- (5.5) transporter 2 (SGLT2) inhibitor, and sitagliptin, a dipeptidyl peptidase-4 • Lower Limb Amputation: Before initiating, consider factors that may (DPP-4) inhibitor, indicated as an adjunct to diet and exercise to increase risk of amputation. Monitor patients for infections or ulcers improve glycemic control in adults with type 2 diabetes mellitus when of lower limbs, and discontinue if these occur. (5.6) treatment with both ertugliflozin and sitagliptin is appropriate. (1) • Heart Failure: Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits in Limitations of Use: patients who have known risk factors for heart failure. Monitor • Not for the treatment of type 1 diabetes mellitus or diabetic patients for signs and symptoms. (5.7) ketoacidosis. (1) • Hypoglycemia: Consider a lower dose of insulin or insulin • Has not been studied in patients with a history of pancreatitis.
    [Show full text]
  • Merck to Present Phase 3 Data on Investigational Medicines ErtugliOzin and MK-1293 at the 76Th ScientiC Sessions of the American Diabetes Association
    NEWS RELEASE Merck to Present Phase 3 Data on Investigational Medicines Ertugliozin and MK-1293 at the 76th Scientic Sessions of the American Diabetes Association 5/12/2016 Additional Analyses from the TECOS Cardiovascular Safety Trial of JANUVIA® (sitagliptin) Also to Be Presented Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that researchers will present data from clinical trials of its investigational diabetes pipeline, JANUVIA® (sitagliptin), and new real-world research in more than 20 scientic data presentations at the 76th Scientic Sessions of the American Diabetes Association (ADA) being held in New Orleans, June 10-14, 2016. New investigational clinical trial data to be presented include the rst Phase 3 results for ertugliozin, an oral SGLT2 inhibitor in development with Pzer for patients with type 2 diabetes, and for MK-1293, Merck’s follow-on biologic insulin glargine candidate being evaluated for patients with type 1 and type 2 diabetes. Additional analyses will also be presented from the TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) cardiovascular safety trial of JANUVIA. “At Merck, we have a long-term commitment to diabetes research and advancing the care of people living with diabetes around the world,” said Peter Stein, M.D., vice president, late stage development, diabetes and endocrinology, Merck. “We look forward to presenting new clinical trial data and results of several studies from real- world settings at this year’s American Diabetes Association Scientic Sessions.” Indications and Usage for JANUVIA (sitagliptin) 25 mg, 50 mg and 100 mg tablets JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes 1 mellitus.
    [Show full text]
  • Effect of Ipragliflozin, an SGLT2 Inhibitor, on Cardiac Histopathological T Changes in a Non-Diabetic Rat Model of Cardiomyopathy ⁎ Toshiyuki Takasu , Shoji Takakura
    Life Sciences 230 (2019) 19–27 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Effect of ipragliflozin, an SGLT2 inhibitor, on cardiac histopathological T changes in a non-diabetic rat model of cardiomyopathy ⁎ Toshiyuki Takasu , Shoji Takakura Drug Discovery Research, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan ARTICLE INFO ABSTRACT Keywords: Aims: We investigated the effect of the selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor Sodium-dependent glucose cotransporter 2 ipragliflozin on cardiac dysfunction and histopathology in a non-diabetic rat model of cardiomyopathy. Ipragliflozin L-proline (PubChem CID: Main methods: Ipragliflozin was mixed with chow (0.01%, w/w) and administered to male DahlS.Z-Leprfa/Leprfa 57339444) (DS/obese) rats for 8 weeks. Male DahlS.Z-Lepr+/Lepr+ (DS/lean) rats of the same age were used as controls. Cardio-protective effect Systolic blood pressure (SBP) and heart rate (HR) were measured every 4 weeks. After 8 weeks of treatment, echocardiography and histopathological examinations were performed. Further, the effect of ipragliflozin on blood and urine parameters were investigated. Key findings: In the DS/obese rats, ipragliflozin delayed the age-related increase in SBP without affecting HR, reduced left ventricular (LV) mass and intraventricular septal thickness in echocardiography, and ameliorated hypertrophy of cardiomyocytes and LV fibrosis in histopathological examination. Although ipragliflozin sig- nificantly increased both urine volume and urinary glucose excretion in DS/obese rats, it did not alterplasma glucose levels. Significance: Ipragliflozin prevented LV hypertrophy and fibrosis in non-diabetic DS/obese rats without affecting plasma glucose levels. These findings suggest that SGLT2 inhibitors have a cardio-protective effect in non-dia- betic patients with cardiomyopathy.
    [Show full text]